The importance of immunologic mediators in both humoral and cell mediated immune reactions is becoming increasingly apparent. A variety of antigen specific and nonantigen specific helper factors have been described recently which can enhance the in vitro antibody responses of normal immunocyte cultures. In this study the role of adjuvant-induced helper factors in the primary antibody response to T-dependent antigens will be assessed for both normal and leukemic cells. Preliminary studies have found that helper factors may be induced from normal cells by lipopolysaccharide (LPS) either in vivo (post-LPS serum) or in vitro (stimulated culture supernatants). Using this as a model for the induction of stimulatory factors, we will correlate the ability to produce antibody response helper factors with the stages of progressive immunodepression in advancing leukemia caused by Friend leukemia virus (FLV). These helper factor responses will be compared with the release of mediators by normal mice or cell cultures. Further studies will determine which immunologic cell types are responsible for the primary production of adjuvant-stimulated antibody helper factors. This should give new insight into the mechanism of immunodepression by a viral leukemia which does not produced suppressor factors. A second related objective is to determine whether the reconstitution of physiological levels of mediators to leukemic mice or cell cultures can compensate for the suppressive effects of the leukemia virus by restoring the immune response capacity to normal levels. Depending upon the results obtained in these studies, the scope of this project will be expanded to include the effects of leukemogenesis upon the production of mediators effecting in vitro correlates of cell mediated immunity such as migration inhibition and blastogenesis.